Efficacy and Safety of Ezetimibe for Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. It is associated with life-threatening conditions such as cardiovascular disease and hepatocellular carcinoma. This systematic review and meta-analysis aimed to evaluate ezetimibe in patients with NAFLD. Methods: A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to August 8th, 2024, to identify relevant articles. The most used keywords for searching are "Ezetimibe" and "Nonalcoholic Fatty Liver Disease." A random-effects model evaluated the standardized mean difference (SMD) and its 95% confidence interval (CI). All analyses were performed using the "meta" package in the R programming language version 4.3.1. Results: Ten studies included in our study (five non-controlled and five controlled trials, with a total of 516 participants) investigated the effect of ezetimibe on different parameters. Ezetimibe significantly improves AST (SMD: -0.63, 95% CI: [-1.12, -0.14]), ALT (SMD: -0.50, 95% CI: [-0.91, -0.10]), GGT (SMD: -0.30, 95% CI: [-0.49, -0.10]), and LDL (SMD: -0.85, 95% CI: [-1.16, -0.54]), but was unable to improve HDL, TG, and BMI. Ezetimibe was also able to improve steatosis (SMD: -0.30, 95% CI: [-0.49, -0.10]), but inflammation (SMD: 0.06, 95% CI: [-0.57, 0.69]), ballooning (SMD: -0.62, 95% CI: [-1.55, 0.31]), and fibrosis (SMD: 0.03, 95% CI: [-0.25, 0.31]) were not improved. Conclusion: Based on the findings, the administration of ezetimibe can reduce liver enzymes as well as the hepatic steatosis, but its effects on liver inflammation and fibrosis remain controversial. Further research is required to study its effects in combination with other treatments.